Understanding Experimental LCMV Infection of Mice: The Role of Mathematical Models

Virus infections represent complex biological systems governed by multiple-level regulatory processes of virus replication and host immune responses. Understanding of the infection means an ability to predict the systems behaviour under various conditions. Such predictions can only rely upon quantitative mathematical models. The model formulations should be tightly linked to a fundamental step called "coordinatization" (Hermann Weyl), that is, the definition of observables, parameters, and structures that enable the link with a biological phenotype. In this review, we analyse the mathematical modelling approaches to LCMV infection in mice that resulted in quantification of some fundamental parameters of the CTL-mediated virus control including the rates of T cell turnover, infected target cell elimination, and precursor frequencies. We show how the modelling approaches can be implemented to address diverse aspects of immune system functioning under normal conditions and in response to LCMV and, importantly, make quantitative predictions of the outcomes of immune system perturbations. This may highlight the notion that data-driven applications of meaningful mathematical models in infection biology remain a challenge. The authors are supported by Grants nos. 15-11-00029 (to Gennady Bocharov and in part Andreas Meyerhans) from the Russian Science Foundation and SAF2013-46077-R (to Andreas Meyerhans and Jordi Argilaguet) from the Spanish Ministry of Economy and Competitiveness and FEDER.